Role of the chromation remodeler protein Chd7 in chondrogenic differentiation of mesenchymal stem cells

• Grant number: 16/24736-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2017
• End date: August 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mari Cleide Sogayar
• Grantee: Bruno Oliveira de Souza
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chromatin remodeler proteins have emerged as critical regulators of chromatin structure, playing a major role during development. Since it was found that CHD7 mutations are the major cause of the CHARGE syndrome in humans, this gene has been further studied from the functional point of view. This syndrome is characterized by a series of congenital malformations, including cranial facial structures, peripheral nervous system, ears, eyes and heart. Different CHD proteins have been already described for being involved in the regulation of stem cells differentiation. It is known that CHD7 homozygous knockout mice die at the embryonic day 11, whereas heterozygous animals are viable and represent an excellent model for studies on CHARGE syndrome. These data highlight the essential role of CHD7 in the process of cell differentiation and normal development of the organism. However, little is known about the molecular mechanism regulation these malformations. In the present study, we aim to investigate the effect of CHD7 downregulation, mediated by shRNA, in the process of mesenchymal stem cells chondrogenic differentiation. We believe that our work may contribute to a better understanding of the molecular mechanisms involved in the malformations characterized in patients with CHARGE syndrome. (AU)